A state-wide initiative to stimulate the research environment in the health-related sciences at the three major research institutions in the State of South Carolina is proposed. Enhancement and sustainable improvements in the capacity for South Carolina institutions to compete successfully for NIH funds will be realized through the development of a facility for generating transgenic mice where, through homologous recombination technology, specific genes will be mutated. Long term objectives include the ability to study in detail the various phenotypes expected to arise from the proposed "knock-out" mice as proposed in ten research projects involving investigators from the Medical University of South Carolina, Clemson University, and the University of South Carolina. The two projects have the following specific aims: Project 1 - to knockout the murine 5-5 glutathione S-transferase in order to study its protective role in hormonal carcinogenesis Project 2 - to develop mice carrying null alleles of the thymidine synthase gene in order to define its role in tumor resistance to 5- fluoropyrimidines All of these projects have relevance to human causes and should provide basic insight into causation and prevention of tumor development.